Sex Differences in the Diagnosis and Treatment of Japanese Patients With Familial Hypercholesterolemia: A Retrospective Cohort Study.

Significant sex differences have been observed in the diagnosis and treatment of familial hypercholesterolemia (FH). This study aimed to clarify sex differences among Japanese FH patients. We assessed Japanese patients who had been clinically diagnosed with heterozygous FH (HeFH) at our hospital from 1990 to 2022 (n=1,273). We compared variables that were associated with the diagnosis and treatment of HeFH and the attainment rate of low-density lipoprotein (LDL)-cholesterol treatment target between male and female patients. We used the Cox proportional hazards model to assess factors associated with major adverse cardiac events (MACEs) between male and female sexes. Female patients diagnosed with HeFH were significantly older than male patients (51 vs. 46 years, p<0.001). The median follow-up period was 10.9 years. Compared with female patients, male patients had significantly lower median LDL-cholesterol levels at baseline (236 vs. 244 mg/dL, p<0.001) and follow-up (110 vs. 116 mg/dL, p<0.001). Female patients with HeFH were less likely to achieve the LDL-cholesterol treatment target than male patients (22% vs. 34%, p<0.001). During the follow-up period, 142 MACEs were observed. Male sex was significantly associated with MACEs (hazard ratio, 1.64; 95% confidence interval, 1.14-2.14; p<0.001). Factors associated with MACEs did not significantly differ between male and female. Female patients with HeFH were diagnosed 5 years later than male patients. Moreover, they were less likely to achieve the guideline-recommended LDL-cholesterol level targets. This sex bias represents a significant barrier to clinical care.